Cassandra N. Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia H. T. Tam, Yasuharu Tabara, Soo-Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor J. Y. Lim, Jin-Fang Chai, Chien-Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K. Iyengar, Hannah J. Perrin, Sarah M. Brotman, Martijn van de Bunt, Anna L. Gloyn, Jennifer E. Below, Michael Boehnke, Donald W. Bowden, John C. Chambers, Anubha Mahajan, Mark I. McCarthy, Maggie C. Y. Ng, Lauren E. Petty, Weihua Zhang, Andrew P. Morris, Linda S. Adair, Masato Akiyama, Zheng Bian, Juliana C. N. Chan, Li-Ching Chang, Miao-Li Chee, Yii-Der Ida Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie-Green Howard, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Masato Isono, Hye-Mi Jang, Guozhi Jiang, Jost B. Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea-Chuen Khor, Katsuhiko Kohara, Myung-Shik Lee, Nanette R. Lee, Liming Li, Jianjun Liu, Andrea O. Luk, Jun Lv, Yukinori Okada, Mark A. Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu-Jen Tsai, Rob M. van Dam, Yong-Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I. Rotter, Ya-Xing Wang, Wayne H. H. Sheu, Mitsuhiro Yokota, Jer-Yuarn Wu, Ching-Yu Cheng, Tien-Yin Wong, Xiao-Ou Shu, Norihiro Kato, Kyong-Soo Park, E-Shyong Tai, Fumihiko Matsuda, Woon-Puay Koh, Ronald C. W. Ma, Shiro Maeda, Iona Y. Millwood, Juyoung Lee, Takashi Kadowaki, Robin G. Walters, Bong-Jo Kim, Karen L. Mohlke, Xueling Sim
Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA, United States; Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan; Division of Genome Research, Center for Genome Science, National Institute of Health, Chungcheongbuk-do, South Korea; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Laboratory for Statistical and Translational Genetics, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan; Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong; Chinese University of Hong Kong-Shanghai Jiao Tong University Joint Research Centre in Diabetes Genomics and Precision Medicine, The Chinese University of Hong Kong, Hong Kong; Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan; The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States; Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance, CA, United States; Biomedical Science, Hallym University, Chuncheon, South Korea; Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, United Kingdom; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, United States; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, United States; Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, United States; Center for Genomics and Personalized Medicine Research, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, United States; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore; Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom; Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom; School of Biological Sciences, University of Manchester, Manchester, United Kingdom; Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Laboratory for Statistical Analysis, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan; Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Chinese Academy of Medical Sciences, Beijing, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore; Division of Endocrinology & Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Institute of Preventive Medicine, School of Public Health, National Taiwan University, Taipei, Taiwan; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, United States; Department of Biostatistics, Carolina Population Center, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China; Division of Endocrine and Metabolism, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan; Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan; Department of Ophthalmology, Medical Faculty Mannheim of the University of Heidelberg, Mannheim, Germany; Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan; Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan; Department of Geriatric and General Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore; Department of Regional Resource Management, Ehime University Faculty of Collaborative Regional Innovation, Ehime, Japan; Severance Biomedical Science Institute and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines; Department of Epidemiology and Biostatistics, Peking University Health Science Centre, Peking University, Beijing, China; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan; Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, United States; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore; Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan; Faculty of Medicine, Macau University of Science and Technology, Macao; Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan; State Key Laboratory of Oncogene and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Medical Biochemistry, Kurume University School of Medicine, Kurume, Japan; Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States; Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Ehime, Japan; Beijing Institute of Ophthalmology, Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Kurume University School of Medicine, Kurume, Japan; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea; Duke-NUS Medical School, Singapore, Singapore; Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore; Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan; Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Okinawa, Japan; Medical Research Council Population Health Research Unit, University of Oxford, Oxford, United Kingdom; Stanford University, Stanford, CA, United States; Genentech, South San Francisco, CA, United States
